The Transplant Pathology and Tissue Imaging Core (Core B) will play a critical, strongly-integrated scientific role in supporting the 2 Projects with strong emphasis on the central focus of the Program. The Program concerns regulatory immune cell therapy using innovative strategies, analysis of underlying mechanisms and novel biomarker studies in NHP renal transplantation. Each Project requires: 1) analysis of routinely-stained slides for pathologic processes relevant to rejection and analyses of allograft tissue from recipients that may exhibit operational tolerance; 2) transplant tissues will be evaluated for cellular and molecular evidence of rejection or tolerance, including the presence and phenotype of APCs, NK cells, effector and regulatory T cell subsets, B cell populations and their expression of molecules relevant to mechanistic aspects of the study and 3) the effects of these cells, molecules and their interactions on surrounding tissues, and vice versa. The Core is ideally suited to conduct these studies because: a) the Core Leader has long-standing experience, including studies on clinical operational tolerance and published extensively (including with other Program investigators in this area; and b) the Core has developed cutting-edge pathology and image analysis tools (multiplex quantum dot immunolabeling combined with high resolution whole slide image (WSI) digital scanning and automated/computerized image analysis that enables more in- depth and objective evaluation of tissue to quantitatively study social/interactive and 3-dimensional relationships between and among various infiltrative cell types and parenchymal and stromal tissues. The principal roles of the Core are: A) Detailed histopathologic assessment of native and allograft tissue specimens, including scoring of standardized histopathologic and immunohistochemical parameters, and rendering diagnoses relevant to rejection/tolerance. B) Specialized multiplex quantum dot-based immunolabeling analyses to localize, quantify, and assess donor- specific effector, memory T cells and Treg responses. In addition, we will seek to validate the Tmem transcription factor eomesodermin as a predictive biomarker of graft rejection vs. tolerance. C) Create high resolution (40x) WSI files so that tissue sections can be reviewed and analyzed, in detail, on a computer screen instead of at a microscope and assist investigators in automated image analysis. D) Prioritize specimen analyses and communicate results and interpretations to the PLs of each project and suggesting alternatives where appropriate; participate in Program investigator meetings, as arranged by Core A.